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| ID | Type | Description | Link |
|---|---|---|---|
| 2010-020904-31 | EudraCT Number |
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This pilot study is designed to evaluate the efficacy, the safety, and the pharmacokinetics (PK) / pharmacodynamics (PD) of canakinumab treatment in patients with HIDS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Canakinumab | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Canakinumab | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Flares Per Participant During Historical Period and Treatment Period | A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a C-reactive protein (CRP) value > 10 mg/L. Flares during a historical period were defined as most recent 6-months in which the participant has not received treatment for their HIDS other than symptomatic treatment with NSAIDs and/or corticosteroids. | Historical period, Month 6 (End of treatment period) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Flares Per Participant at During Treatment Period and 24 Month Extension Period | A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L. | Month 6 (End of treatment period), Month 36 (End of Long term treatment Period 2) |
| Number of Participants Who Flared at Month 6, Month 24 and Month 36 |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Other protocol-defined inclusion/exclusion criteria may apply
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| Name | Affiliation | Role |
|---|---|---|
| Novartis Pharmaceuticals | Novartis Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Esplugues de Llobregat | Barcelona | 08950 | Spain | ||
| Novartis Investigative Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28482144 | Derived | Arostegui JI, Anton J, Calvo I, Robles A, Iglesias E, Lopez-Montesinos B, Banchereau R, Hong S, Joubert Y, Junge G, Pascual V, Yague J. Open-Label, Phase II Study to Assess the Efficacy and Safety of Canakinumab Treatment in Active Hyperimmunoglobulinemia D With Periodic Fever Syndrome. Arthritis Rheumatol. 2017 Aug;69(8):1679-1688. doi: 10.1002/art.40146. Epub 2017 Jul 5. |
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A total of 10 participants were screened, 9 of which entered in the treatment period of the study, one participant was considered to be a screening failure.
The study was conducted at 3 centres in Spain.
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| ID | Title | Description |
|---|---|---|
| FG000 | Canakinumab | Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new Hyper-IgD with periodic fever syndrome (HIDS) flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
The analysis was performed in the Full Analysis Set (FAS), defined as all participants who received at least one application of study treatment and had at least one post-baseline assessment for primary efficacy variable.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Canakinumab | Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Flares Per Participant During Historical Period and Treatment Period | A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a C-reactive protein (CRP) value > 10 mg/L. Flares during a historical period were defined as most recent 6-months in which the participant has not received treatment for their HIDS other than symptomatic treatment with NSAIDs and/or corticosteroids. | The primary analysis was performed in the Full Analysis set (FAS) population defined as all participants who received at least one dose of study treatment and had at least one post baseline assessment. | Posted | Median | Full Range | Number of flares | Historical period, Month 6 (End of treatment period) |
|
Serious Adverse Events are monitored from date of First Participant First Visit (FPFV) until Last Participant Last Visit (LPLV). All other adverse events are monitored from First Participant First Treatment until LPLV.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Canakinumab | Participants received body weight stratified dosage of canakinumab (4 mg/kg for participants less than or equal to (≤) 40 kg or 300 mg for participants more than (>) 40 kg) as starting dose s.c. injection every 6 weeks during 6 months of treatment. The dose was escalated to additional 150 mg (2 mg/kg for participants ≤40 kg) dose at the moment of flare, and 450 mg (6 mg/kg for participants ≤40 kg) every 6 weeks, thereafter starting at Week 6 in participants who experienced a new HIDS flare between baseline and Week 4 as per investigator's discretion. If the flare occurred between Weeks 5-6, the participants received rescue medication and waited up to Week 6 to receive a total of 450 mg of canakinumab. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tachycardia | Cardiac disorders | MedDRA | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Novartis Pharmaceuticals | 862 -778 -8300 |
Not provided
| ID | Term |
|---|---|
| D054078 | Mevalonate Kinase Deficiency |
| ID | Term |
|---|---|
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
Not provided
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| ID | Term |
|---|---|
| C541220 | canakinumab |
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A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L. |
| Baseline, Month 6 (End of treatment period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Physician global assessment of severity of HIDS after each flare was based on HIDS flare severity score, a 5- point scale: 0 = Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3= Moderate; 4 = Severe. | Any flare event [Baseline up to Month 36 (End of long term treatment period 2)] |
| Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Participant's global assessment of severity of HIDS after each flare was based on HIDS flare severity score, a 5-point scale: 0 = Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3= Moderate; 4 = Severe. Same investigator assessed the same participant throughout the study to ensure consistency between assessments. Investigators reviewed every participant's diary at each visit after their own clinical assessment. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Participants were assessed by participants/parent (participants aged 6-18 years) for control of signs and symptoms associated with HIDS based on 5-point scale: 0 = No control; 1 = Poor control; 2 = Somewhat control; 3 = Good control; and 4= Excellent control. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Participants were assessed by physician for control of signs and symptoms associated with HIDS based on 5-point scale: 0 = No control; 1 = Poor control; 2 = Somewhat control; 3 = Good control; and 4= Excellent control. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Fever severity was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Apthus ulcers were assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Lymphadenopathy severity was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Abdominal pain was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Time to Resolution of the Initial Flare After First Canakinumab Treatment | Time to resolution of the initial flare after first dose of canakinumab was determined. | Day 1 (Baseline), Day 28 |
| Change From Baseline in Inflammation Markers Over Time up to Month 24 | The C-reactive Protein (CRP) and/or Serum amyloid A protein (SAA) were used as inflammatory markers. The normal range of CRP was 0-10 mg/L. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Health Assessment Questionnaire (HAQ) Global Score in Adults Over Time | Participants were assessed for health-related quality of life (HRQoL) based on Health Assessment Questionnaire (HAQ). HAQ was an eight 8 categories questionnaire representing all activities related to physical function. Each category has various sub-categories, which were rated by the participants on a 4- point difficulty scale: 0 = any difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. The total score was the mean of the 8 scores, and ranged from 0 (no disability) to 3 (completely disabled). | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Childhood Health Assessment Questionnaire (CHAQ) Global Score in Children Over Time | Participants or their parents (participants aged 6 to 17 years) were assessed for HRQoL based on Childhood Health Assessment Questionnaire (CHAQ). CHAQ was an eight domain questionnaire representing functional capacity and independence, evaluated for previous week. Each domain was rated on a 4-point difficulty scale: 0 = any difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do.The total score is the mean from the 8 scores, and ranges from 0 (no disability) to 3 (completely disabled). | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Percentage of Participants Who Received Dose Up-titration During 6-month Treatment Period | Participants who experienced a new HIDS flare between baseline and Week 4 and received an escalated dose of 450 mg of canakinumab every 6 weeks thereafter starting at Week 6 were determined. | Day 1 up to Month 6 (End of follow up) |
| Duration of Flares Experienced During the Study | Flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L. The change in post canakinumab treatment flare duration during the study were assessed as compared to historical period. | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
| Time to Flare After the Last Dose of Canakinumab During the Follow-up Period | The median time to flare by the participants after administration of the last dose of canakinumab during the follow-up period was analysed using Kaplan-Meier method. | Last dose of canakinumab treatment in follow-up period to end of follow-up period (Day 337) |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalisation, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. | Day 1 (Start of study treatment) up to Month 36 (End of study) |
| Participants Who Received Rescue Treatment | Participants who experienced flares were treated with corticosteroids and NSAIDs as rescue medication. | Baseline up to Month 36 (End of study) |
| Serum Concentration-time Profile of Canakinumab | Canakinumab concentrations in serum were assessed for evaluating pharmacokinetics (PK) of the drug. | Day 1 (Pre-dose), Day 4, Day 15, Day 43, Day 85, Day 127, Day 169 (End of treatment period), Day 197, Day 225, Day 253, Day 281, Day 309, and Day 337 (End of follow-up period) (Post-dose) |
| Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Pharmacodynamics of canakinumab was assessed by total IL-1β (sum of free and bound canakinumab) concentration, determined in serum by means of sandwich ELISA assay with limit of detection at 0.1 picogram/millilitre. | Day 1 (Pre-dose), Day 4, Day 15, Day 43, Day 85, Day 127, Day 169 (End of treatment period), Day 197, Day 225, Day 253, Day 281, Day 309, and Day 337 (End of follow-up period) (Post-dose) |
| Number of Participants Exhibiting Anti-canakinumab Antibodies at Any Visit | Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using bridging ECLIA assay. | Baseline up to Month 36 (End of study) |
| Madrid |
| Madrid |
| 28046 |
| Spain |
| Novartis Investigative Site | Valencia | Valencia | 46026 | Spain |
| years |
|
| Age, Customized | Number | participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Number of Flares Per Participant at During Treatment Period and 24 Month Extension Period | A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L. | The analysis was performed in the FAS population. | Posted | Median | Full Range | Number of flares | Month 6 (End of treatment period), Month 36 (End of Long term treatment Period 2) |
|
|
|
| Secondary | Number of Participants Who Flared at Month 6, Month 24 and Month 36 | A flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L. | The analysis was performed in the FAS population. | Posted | Number | Number of participants | Baseline, Month 6 (End of treatment period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
|
|
|
| Secondary | Number of Participants With Flare Events Based on Physician Assessed HIDS Flare Severity Score | Physician global assessment of severity of HIDS after each flare was based on HIDS flare severity score, a 5- point scale: 0 = Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3= Moderate; 4 = Severe. | The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively. | Posted | Number | Number of participants | Any flare event [Baseline up to Month 36 (End of long term treatment period 2)] |
|
|
|
| Secondary | Number of Participants With Flare Events Based on Participant Assessed HIDS Flare Severity Score | Participant's global assessment of severity of HIDS after each flare was based on HIDS flare severity score, a 5-point scale: 0 = Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3= Moderate; 4 = Severe. Same investigator assessed the same participant throughout the study to ensure consistency between assessments. Investigators reviewed every participant's diary at each visit after their own clinical assessment. | The analysis was performed in the FAS population. | Posted | Number | Number of participants | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
|
|
|
| Secondary | Percentage of Participants With Defined Grades of Participants Assessed Symptom Control | Participants were assessed by participants/parent (participants aged 6-18 years) for control of signs and symptoms associated with HIDS based on 5-point scale: 0 = No control; 1 = Poor control; 2 = Somewhat control; 3 = Good control; and 4= Excellent control. | The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively. | Posted | Number | Percentage of participants | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
|
|
|
| Secondary | Percentage of Participants With Defined Grades of Physician Assessed Symptom Control | Participants were assessed by physician for control of signs and symptoms associated with HIDS based on 5-point scale: 0 = No control; 1 = Poor control; 2 = Somewhat control; 3 = Good control; and 4= Excellent control. | The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively. | Posted | Number | Percentage of participants | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
|
|
|
| Secondary | Percentage of Participants Experiencing Fever as Assessed by Physician's Global Assessment | Fever severity was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe. | The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively. | Posted | Number | Percentage of participants | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
|
|
|
| Secondary | Percentage of Participants Experiencing Apthus Ulcers as Assessed by Physician's Global Assessment | Apthus ulcers were assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe. | The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively. | Posted | Number | Percentage of participants | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
|
|
|
| Secondary | Percentage of Participants Experiencing Lymphadenopathy as Assessed by Physician's Global Assessment | Lymphadenopathy severity was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe. | The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively. | Posted | Number | Percentage of participants | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
|
|
|
| Secondary | Percentage of Participants Experiencing Abdominal Pain as Assessed by Physician's Global Assessment | Abdominal pain was assessed by physician after each flare using a 5-point scale: 0 =Absent signs/symptoms; 1 = Minimal signs/symptoms; 2 = Mild; 3 = Moderate; 4 = Severe. | The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group, respectively. | Posted | Number | Percentage of participants | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
|
|
|
| Secondary | Time to Resolution of the Initial Flare After First Canakinumab Treatment | Time to resolution of the initial flare after first dose of canakinumab was determined. | The analysis was performed in the FAS population. | Posted | Median | Full Range | Days | Day 1 (Baseline), Day 28 |
|
|
|
| Secondary | Change From Baseline in Inflammation Markers Over Time up to Month 24 | The C-reactive Protein (CRP) and/or Serum amyloid A protein (SAA) were used as inflammatory markers. The normal range of CRP was 0-10 mg/L. | The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group respectively. | Posted | Median | Full Range | milligram(s)/liter | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
|
|
|
| Secondary | Health Assessment Questionnaire (HAQ) Global Score in Adults Over Time | Participants were assessed for health-related quality of life (HRQoL) based on Health Assessment Questionnaire (HAQ). HAQ was an eight 8 categories questionnaire representing all activities related to physical function. Each category has various sub-categories, which were rated by the participants on a 4- point difficulty scale: 0 = any difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do. The total score was the mean of the 8 scores, and ranged from 0 (no disability) to 3 (completely disabled). | The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group respectively. Here "Number of participants analyzed" signifies the participants assessed for HAQ during study. | Posted | Median | Full Range | Score on a scale | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
|
|
|
| Secondary | Childhood Health Assessment Questionnaire (CHAQ) Global Score in Children Over Time | Participants or their parents (participants aged 6 to 17 years) were assessed for HRQoL based on Childhood Health Assessment Questionnaire (CHAQ). CHAQ was an eight domain questionnaire representing functional capacity and independence, evaluated for previous week. Each domain was rated on a 4-point difficulty scale: 0 = any difficulty; 1 = some difficulty; 2 = much difficulty; 3 = unable to do.The total score is the mean from the 8 scores, and ranges from 0 (no disability) to 3 (completely disabled). | The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group respectively. Here "Number of participants analyzed" signifies the participants assessed for CHAQ during study. | Posted | Median | Full Range | Score on a scale | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
|
|
|
| Secondary | Percentage of Participants Who Received Dose Up-titration During 6-month Treatment Period | Participants who experienced a new HIDS flare between baseline and Week 4 and received an escalated dose of 450 mg of canakinumab every 6 weeks thereafter starting at Week 6 were determined. | The analysis was performed in the FAS population. | Posted | Number | Percentage of participants | Day 1 up to Month 6 (End of follow up) |
|
|
|
| Secondary | Duration of Flares Experienced During the Study | Flare was defined as Physician Global Assessment of HIDS flare severity score of ≥ 2 and a CRP value > 10 mg/L. The change in post canakinumab treatment flare duration during the study were assessed as compared to historical period. | The analysis was performed in the FAS population. The 'n' signifies those participants evaluable for this measure at specified time points for each group respectively. | Posted | Median | Full Range | Days | Baseline, Month 6 (End of treatment period), Month 12 (End of follow up period), Month 24 (End of Long term treatment period 1) and Month 36 (End of Long term treatment period 2) |
|
|
|
| Secondary | Time to Flare After the Last Dose of Canakinumab During the Follow-up Period | The median time to flare by the participants after administration of the last dose of canakinumab during the follow-up period was analysed using Kaplan-Meier method. | The analysis was performed on the FAS population. Here "Number of participants analysed" signifies the participants assessed for time to flare after the last dose of canakinumab during follow-up period. | Posted | Median | Full Range | days | Last dose of canakinumab treatment in follow-up period to end of follow-up period (Day 337) |
|
|
|
| Secondary | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Adverse events (AEs) were defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events (SAEs) were defined as any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalisation, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgement of investigators represent significant hazards. | The analysis was performed on Safety Set (SAF) population defined as all participants who received at least one application of study treatment and had at least one post-baseline safety assessment. | Posted | Number | Number of participants | Day 1 (Start of study treatment) up to Month 36 (End of study) |
|
|
|
| Secondary | Participants Who Received Rescue Treatment | Participants who experienced flares were treated with corticosteroids and NSAIDs as rescue medication. | The analysis was performed on the FAS population. | Posted | Number | Percentage of participants | Baseline up to Month 36 (End of study) |
|
|
|
| Secondary | Serum Concentration-time Profile of Canakinumab | Canakinumab concentrations in serum were assessed for evaluating pharmacokinetics (PK) of the drug. | The analysis was performed on the FAS population. | Posted | Mean | Standard Deviation | microgram(s)/milliliter | Day 1 (Pre-dose), Day 4, Day 15, Day 43, Day 85, Day 127, Day 169 (End of treatment period), Day 197, Day 225, Day 253, Day 281, Day 309, and Day 337 (End of follow-up period) (Post-dose) |
|
|
|
| Secondary | Serum Concentration of Total Interleukin-1β Antibody (IL-1β) | Pharmacodynamics of canakinumab was assessed by total IL-1β (sum of free and bound canakinumab) concentration, determined in serum by means of sandwich ELISA assay with limit of detection at 0.1 picogram/millilitre. | The analysis was performed on the FAS population. | Posted | Mean | Standard Deviation | picogram(s)/milliliter | Day 1 (Pre-dose), Day 4, Day 15, Day 43, Day 85, Day 127, Day 169 (End of treatment period), Day 197, Day 225, Day 253, Day 281, Day 309, and Day 337 (End of follow-up period) (Post-dose) |
|
|
|
| Secondary | Number of Participants Exhibiting Anti-canakinumab Antibodies at Any Visit | Immunogenicity assessment included determination of anti-canakinumab (ACZ885) antibodies in serum samples using bridging ECLIA assay. | The analysis was performed on the FAS population. | Posted | Number | Number of participants | Baseline up to Month 36 (End of study) |
|
|
|
| 4 |
| 9 |
| 9 |
| 9 |
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Disease progression | General disorders | MedDRA | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Peritonitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA | Systematic Assessment |
|
| Streptococcal bacteraemia | Infections and infestations | MedDRA | Systematic Assessment |
|
| Fluid overload | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Temporomandibular joint syndrome | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Hidradenitis | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Hypertensive crisis | Vascular disorders | MedDRA | Systematic Assessment |
|
| Conjunctival hyperaemia | Eye disorders | MedDRA | Systematic Assessment |
|
| Conjunctivitis | Eye disorders | MedDRA | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA | Systematic Assessment |
|
| Impaired healing | General disorders | MedDRA | Systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA | Systematic Assessment |
|
| Pyrexia | General disorders | MedDRA | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Candidiasis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Folliculitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Impetigo | Infections and infestations | MedDRA | Systematic Assessment |
|
| Infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Pharyngotonsillitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA | Systematic Assessment |
|
| Tonsillitis streptococcal | Infections and infestations | MedDRA | Systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Vulvovaginal mycotic infection | Infections and infestations | MedDRA | Systematic Assessment |
|
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Scoliosis | Musculoskeletal and connective tissue disorders | MedDRA | Systematic Assessment |
|
| Bone neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA | Systematic Assessment |
|
| Vaginal ulceration | Reproductive system and breast disorders | MedDRA | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA | Systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Eczema | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Erythema nodosum | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Hidradenitis | Skin and subcutaneous tissue disorders | MedDRA | Systematic Assessment |
|
| Tooth extraction | Surgical and medical procedures | MedDRA | Systematic Assessment |
|
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single site are postponed until the publication of the pooled data (i.e, data from all sites) in the clinical trial.
| D009422 | Nervous System Diseases |
| D006942 | Hypergammaglobulinemia |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D056660 | Hereditary Autoinflammatory Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008661 | Metabolism, Inborn Errors |
| D018901 | Peroxisomal Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
|
| Day 45,Moderate (n=9) |
|
| Day 45,Severe (n=9) |
|
| Flare/Unscheduled visit 1, Absent (n=2) |
|
| Flare/Unscheduled visit 1, Minimal (n=2) |
|
| Flare/Unscheduled visit 1, Mild (n=2) |
|
| Flare/Unscheduled visit 1, Moderated (n=2) |
|
| Flare/Unscheduled visit 1, Severe (n=2) |
|
| Flare/Unscheduled visit 2, Absent (n=2) |
|
| Flare/Unscheduled visit 2, Minimal (n=2) |
|
| Flare/Unscheduled visit 2, Mild (n=2) |
|
| Flare/Unscheduled visit 2, Moderate (n=2) |
|
| Flare/Unscheduled visit 2, Severe (n=2) |
|
| Flare/Unscheduled visit 3, Absent (n=2) |
|
| Flare/Unscheduled visit 3, Minimal (n=2) |
|
| Flare/Unscheduled visit 3, Mild (n=2) |
|
| Flare/Unscheduled visit 3, Moderate (n=2) |
|
| Flare/Unscheduled visit 3, Severe (n=2) |
|
| End of Treatment period, Absent (n=7) |
|
| End of Treatment period, Minimal (n=7) |
|
| End of Treatment period, Mild (n=7) |
|
| End of Treatment period, Moderate (n=7) |
|
| End of Treatment period, Severe (n=7) |
|
| End of Follow-up period, Absent (n=8) |
|
| End of Follow-up period, Minimal (n=8) |
|
| End of Follow-up period, Mild (n=8) |
|
| End of Follow-up period, Moderate (n=8) |
|
| End of Follow-up period, Severe (n=8) |
|
| Long term period 1, Flare 1, Absent (n=3) |
|
| Long term period 1, Flare 1, Minimal (n=3) |
|
| Long term period 1, Flare 1, Mild (n=3) |
|
| Long-term 12 M period, Flare 1, Moderate (n=3) |
|
| Long-term 12 M period, Flare 1, Severe (n=3) |
|
| Long term period 1, Flare 2, Absent (n=1) |
|
| Long-term 12 M period, Flare 2, Minimal (n=1) |
|
| Long-term 12 M period, Flare 2, Mild (n=1) |
|
| Long term period 1, Flare 2, Moderate (n=1) |
|
| Long term period 1, Flare 2, Severe (n=1) |
|
| Long term period 1, Flare 3, Absent (n=1) |
|
| Long term period 1, Flare 3, Minimal (n=1) |
|
| Long term period 1, Flare 3, Mild (n=1) |
|
| Long term period 1, Flare 3, Moderate (n=1) |
|
| Long term period 1, Flare 3, Severe (n=1) |
|
| Long term period 2, Absent (n=2) |
|
| Long term period 2, Minimal (n=2) |
|
| Long term period 2, Mild (n=2) |
|
| Long term period 2, Moderate (n=2) |
|
| Long term period 2, Severe (n=2) |
|
| Title | Measurements |
|---|---|
|
| Treatment period, Moderate |
|
| Treatment period, Severe |
|
| Follow-up period, Absent |
|
| Follow-up period, Minimal |
|
| Follow-up period, Mild |
|
| Follow-up period, Moderate |
|
| Follow-up period, Severe |
|
| Long term period 1, Absent |
|
| Long term period 1, Minimal |
|
| Long term period 1, Mild |
|
| Long term period 1, Moderate |
|
| Long term period 1, Severe |
|
| Long term period 2, Absent |
|
| Long term period 2, Minimal |
|
| Long term period 2, Mild |
|
| Long term period 2, Moderate |
|
| Long term period 2, Severe |
|
| Title | Measurements |
|---|---|
|
| Treatment period, Good control (n=9) |
|
| Treatment period, Excellent control (n=9) |
|
| Follow-up period, No control (n=9) |
|
| Follow-up period, Poor control (n=9) |
|
| Follow-up period, Somewhat control (n=9) |
|
| Follow-up period, Good control (n=9) |
|
| Follow-up period, Excellent control (n=9) |
|
| Long term period 1, No control (n=8) |
|
| Long term period 1, Poor control (n=8) |
|
| Long term period 1, Somewhat control (n=8) |
|
| Long term period 1, Good control (n=8) |
|
| Long term period 1, Excellent control (n=8) |
|
| Long term period 2, No control (n=8) |
|
| Long term period 2, Poor control (n=8) |
|
| Long term period 2, Somewhat control (n=8) |
|
| Long term period 2, Good control (n=8) |
|
| Long term period 2, Excellent control (n=8 |
|
| Title | Measurements |
|---|---|
|
| Treatment period, Good control (n=9) |
|
| Treatment period, Excellent control (n=9) |
|
| Follow-up period, No control (n=9) |
|
| Follow-up period, Poor control (n=9) |
|
| Follow-up period, Somewhat control (n=9) |
|
| Follow-up period, Good control (n=9) |
|
| Follow-up period, Excellent control (n=9) |
|
| Long term period 1, No control (n=8) |
|
| Long term period 1, Poor control (n=8) |
|
| Long term period 1, Somewhat control (n=8) |
|
| Long term period 1, Good control (n=8) |
|
| Long term period 1, Excellent control (n=8) |
|
| Long term period 2, No control (n=8) |
|
| Long term period 2, Poor control (n=8) |
|
| Long term period 2, Somewhat control (n=8) |
|
| Long term period 2, Good control (n=8) |
|
| Long term period 2, Excellent control (n=8 |
|
| Title | Measurements |
|---|---|
|
| Treatment period, Moderate (n=9) |
|
| Treatment period, Severe (n=9) |
|
| Follow-up period, Absent (n=9) |
|
| Follow-up period, Minimal (n=9) |
|
| Follow-up period, Mild (n=9) |
|
| Follow-up period, Moderate (n=9) |
|
| Follow-up period, Severe (n=9) |
|
| Long term period 1, Absent (n=8) |
|
| Long term period 1, Minimal (n=8) |
|
| Long term period 1, Mild (n=8) |
|
| Long term period 1, Moderate (n=8) |
|
| Long term period 1, Severe (n=8) |
|
| Long term period 2, Absent (n=8) |
|
| Long term period 2, Minimal (n=8) |
|
| Long term period 2, Mild (n=8) |
|
| Long term period 2, Moderate (n=8) |
|
| Long term period 2, Severe (n=8) |
|
| Title | Measurements |
|---|---|
|
| Treatment period, Moderate (n=9) |
|
| Treatment period, Severe (n=9) |
|
| Follow-up period, Absent (n=9) |
|
| Follow-up period, Minimal (n=9) |
|
| Follow-up period, Mild (n=9) |
|
| Follow-up period, Moderate (n=9) |
|
| Follow-up period, Severe (n=9) |
|
| Long term period 1, Absent (n=8) |
|
| Long term period 1, Minimal (n=8) |
|
| Long term period 1, Mild (n=8) |
|
| Long term period 1, Moderate (n=8) |
|
| Long term period 1, Severe (n=8) |
|
| Long term period 2, Absent (n=8) |
|
| Long term period 2, Minimal (n=8) |
|
| Long term period 2, Mild (n=8) |
|
| Long term period 2, Moderate (n=8) |
|
| Long term period 2, Severe (n=8) |
|
| Title | Measurements |
|---|---|
|
| Treatment period, Moderate (n=9) |
|
| Treatment period, Severe (n=9) |
|
| Follow-up period, Absent (n=9) |
|
| Follow-up period, Minimal (n=9) |
|
| Follow-up period, Mild (n=9) |
|
| Follow-up period, Moderate (n=9) |
|
| Follow-up period, Severe (n=9) |
|
| Long term period 1, Absent (n=8) |
|
| Long term period 1, Minimal (n=8) |
|
| Long term period 1, Mild (n=8) |
|
| Long term period 1, Moderate (n=8) |
|
| Long term period 1, Severe (n=8) |
|
| Long term period 2, Absent (n=8) |
|
| Long term period 2, Minimal (n=8) |
|
| Long term period 2, Mild (n=8) |
|
| Long term period 2, Moderate (n=8) |
|
| Long term period 2, Severe (n=8) |
|
| Title | Measurements |
|---|---|
|
| Treatment period, Moderate (n=9) |
|
| Treatment period, Severe (n=9) |
|
| Follow-up period, Absent (n=9) |
|
| Follow-up period, Minimal (n=9) |
|
| Follow-up period, Mild (n=9) |
|
| Follow-up period, Moderate (n=9) |
|
| Follow-up period, Severe (n=9) |
|
| Long term period 1, Absent (n=8) |
|
| Long term period 1, Minimal (n=8) |
|
| Long term period 1, Mild (n=8) |
|
| Long term period 1, Moderate (n=8) |
|
| Long term period 1, Severe (n=8) |
|
| Long term period 2, Absent (n=8) |
|
| Long term period 2, Minimal (n=8) |
|
| Long term period 2, Mild (n=8) |
|
| Long term period 2, Moderate (n=8) |
|
| Long term period 2, Severe (n=8) |
|
|
| CRP- Long term period 2, (n=8) |
|
| SAA- 6 month (Treatment period), (n=1) |
|
| SAA- 6 month (Follow-up period), (n=2) |
|
| SAA- Long term period 1, (n=2) |
|
| SAA- Long term period 2, (n=2) |
|
| Title | Measurements |
|---|---|
|
| Long term period 2, (n=4) |
|
|
| Long term period 2, (n=1) |
|
| Title | Measurements |
|---|---|
|
| Long term period 2, (n=2) |
|
| Title | Measurements |
|---|---|
|
| Day 85 |
|
| Day 127 |
|
| Day 169 |
|
| Day 197 |
|
| Day 225 |
|
| Day 253 |
|
| Day 281 |
|
| Day 309 |
|
| Day 337 |
|
| Title | Measurements |
|---|---|
|
| Day 85 |
|
| Day 127 |
|
| Day 169 |
|
| Day 197 |
|
| Day 225 |
|
| Day 253 |
|
| Day 281 |
|
| Day 309 |
|
| Day 337 |
|